Click Chemistry-Enabled Analytical Strategies for Food Safety, Quality, and Authenticity: Mechanistic Insights, Technological Advances, and Future Perspectives

Achieving food safety, quality, and authenticity need analytical strategies that can meet the challenges introduced by more complex matrices and ultra-trace contaminants. Recently, click-chemistry which has the attributes of selectivity, modularity, and rapid kinetics has emerged as powerful tool for food analytical science. This review highlights the role of click chemistry in various steps of the food analytical workflow, including sample preparation, sorbent engineering, signal amplification, and sensor-based detection. A significant focus will be placed on reaction mechanisms, improve analytical performance and real-world applicability along with a systematic overview of current limitations and associated regulatory challenges. This utilizes stable conjugation, efficient tagging, and tailored material functionalization to provide enhanced analytical selectivity, sensitivity, and reproducibility via click-enabled strategies. Such applications in sorbent design and molecular imprinting lead to higher extraction efficiency and tolerance toward matrix, while the redesign of click-mediated labeling approaches facilitates great improvements in both ionization efficiency and quantitative reliability for mass spectrometry. Moreover, the compatibility with optical and electrochemical sensors enables rapid and portable detection platforms. Notwithstanding these improvements, several hurdles remain, such as catalyst toxicity, matrix effects and interference, limits to scalability, high costs of substrates/reagents used in the sensors, and need for standardization of validation protocols. Wider implementation is further constrained by regulatory gaps and lack of acceptance for non-targeted and AI-assisted methodologies. Click-chemistry in future will be integrated with miniaturized, automatized, and data-driven systems for enable real-time, decentralized monitoring of food.